Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release.
Neurotransmitter release from presynaptic nerve terminals is regulated by soluble NSF attachment protein receptor (SNARE) complex-mediated synaptic vesicle fusion. Tomosyn inhibits SNARE complex formation and neurotransmitter release by sequestering syntaxin-1 through its C-terminal vesicle-associated membrane protein (VAMP)-like domain (VLD). However, in tomosyn-deficient mice, the SNARE complex formation is unexpectedly decreased. In this study, we demonstrate that the N-terminal WD-40 repeat domain of tomosyn catalyzes the oligomerization of the SNARE complex. Microinjection of the tomosyn N-terminal WD-40 repeat domain into neurons prevented stimulated acetylcholine release. Thus, tomosyn inhibits neurotransmitter release by catalyzing oligomerization of the SNARE complex through the N-terminal WD-40 repeat domain in addition to the inhibitory activity of the C-terminal VLD.
Sakisaka
Toshiaki
T
Division of Membrane Dynamics, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Yamamoto
Yasunori
Y
Mochida
Sumiko
S
Nakamura
Michiko
M
Nishikawa
Kouki
K
Ishizaki
Hiroyoshi
H
Okamoto-Tanaka
Miki
M
Miyoshi
Jun
J
Fujiyoshi
Yoshinori
Y
Manabe
Toshiya
T
Takai
Yoshimi
Y
D000818:Animals; D008297:Male; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D009473:Neuronal Plasticity; D018377:Neurotransmitter Agents / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D050683:R-SNARE Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020449:Repetitive Sequences, Amino Acid; D050600:SNARE Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D013329:Structure-Activity Relationship; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D050827:Syntaxin 1 / Q000378:metabolism
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; C112618:tomosyn protein, mouse